Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility

Area of Science:

• Immunology
• Endocrinology
• Genomics

Background:

• Autoimmune thyroid diseases (AITDs) like Hashimoto thyroiditis and Graves disease are more common in women.
• The role of plasma B cells in thyroid autoimmunity and their presence in healthy female thyroids is not well understood.

Purpose of the Study:

• To investigate plasma B cell infiltration in female thyroid tissue without clinical autoimmune disease.
• To identify molecular mechanisms driving plasma B cell presence in the female thyroid.

Main Methods:

• Bulk RNA-sequencing (RNA-seq) to analyze gene expression differences.
• Single-cell RNA-seq and spatial transcriptomics to pinpoint cell types and locations.
• Analysis focused on identifying sex-specific gene expression patterns related to B cells.

Main Results:

• Significant sex differences were observed in thyroid gene expression, particularly for B cell-related genes.
• The CXCL13-CXCR5 signaling pathway was identified as crucial for recruiting and organizing plasma B cells in the thyroid.
• Plasma B cells were found in female thyroid tissue even in the absence of clinical autoimmune disease.

Conclusions:

• The inherent presence of plasma B cells in the female thyroid, mediated by CXCL13, may predispose women to AITDs.
• Understanding sex-specific immune cell distribution is vital for explaining differential disease prevalence.
• This study offers novel insights into the female thyroid immune microenvironment and autoimmunity risk.